Cell culture and mouse
studies suggest inhibiting RSK3 and RSK4 could be useful for treating breast
cancers resistant to PI3K inhibitors. In cultured breast cancer cells,
vector-mediated overexpression of RSK3 or RSK4 increased cell survival in the
presence of PI3K pathway inhibitors compared with a control vector. In mouse
xenograft models for human breast cancer, vector-mediated overexpression of
RSK3 or RSK4 decreased tumor sensitivity to PI3K inhibitors compared with no
overexpression. Next steps include identifying selective inhibitors of RSK3
and RSK4 and evaluating them in PI3K inhibitor-resistant tumors.

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